A case report of Paracetamol related pyroglutamic acidosis: mind the gap in a malnourished patient.

BACKGROUND: Pyroglutamic acidosis is a rare cause of high anion gap metabolic acidosis. Most cases of paracetamol related pyroglutamic acidosis are described in malnourished women and patients with kidney/liver failure, alcohol use or severe sepsis. In this report, we describe how pyroglutamic acidosis could be related to the use of chronic therapeutic paracetamol with only malnutrition as an associated risk factor. CASE PRESENTATION: We report a case of a 67-year-old male patient developing a pyroglutamic acidosis. The patient was initially admitted to hospital for infectious osteoarthritis and developed a metabolic acidosis during his hospital stay. Analgesics included daily therapeutic doses of paracetamol. What makes our case unusual is that our malnourished male patient did not have renal or hepatic failure. The diagnosis of paracetamol related pyroglutamic acidosis was made after ruling out the main causes of metabolic acidosis. It was further confirmed by urine organic acids measurement showing a markedly elevated level of pyroglutamic aciduria. Paracetamol was discontinued allowing a prompt correction of the anion gap. CONCLUSION: This case is a representative of pyroglutamic acidosis related to chronic therapeutic paracetamol with only malnutrition as an associated risk factor. Physicians should be aware of such unusual cause of metabolic acidosis, which may be more common than expected in hospitalized patients. A high clinical suspicion is needed when urine organic acids analysis is not available.

Analysis of physical traits, clinical parameters, and energy metabolism of in vivo- and in vitro-derived Flemish newborn calves during the first day of life.

Studies investigating physiological deviations from normality in newborn calves derived from in vitro fertilization procedures remain important for the understanding of factors that reduce calf survival after birth. The aim of this study was to investigate parameters affecting health and welfare of newborn Flemish calves derived from in vitro embryo production (IVP) in the first hours of life in comparison to in vivo-derived calves. Physical traits of newborn calves and fetal membranes (FM) were recorded soon after birth. Newborn venous blood samples were collected at several time points within the first 24 h of life for analyses of energy substrates, electrolytes, blood gases, acid-base balance, blood chemistry, and haematology. A liver biopsy was taken within the first hour after birth for analysis of gene expression of key enzymes of the fructolytic and glycolytic pathways. Newborn IVP calves were heavier and larger at birth, which was associated with heavier FM. At several time points during the first 24 h of life, IVP-derived calves had altered rectal temperature, blood gases, electrolyte concentrations, blood parameters for liver, kidney and muscle function, and acid-base balance, plasma lipid metabolism, and hemogram parameters. The relative mRNA abundances for triokinase and lactate dehydrogenase-B were greater in IVP calves. In summary, IVP-derived newborn calves were at higher risk of clinical problems after birth, which was markedly greater in heavier and larger calves. Such animals take longer to adapt to extrauterine life and should receive a special attention during the immediate neonatal period.

Association between the anion-gap and 28-day mortality in critically ill adult patients with sepsis: A retrospective cohort study.

Metabolic acidosis is usually associated with the severity of the condition of patients with sepsis or septic shock. Serum anion gap (AG) is one of the indicators of response metabolism. This study was performed to investigate whether the initial serum AG is associated with the 28-day mortality in critically ill adult patients with sepsis. This retrospective cohort study, a total of 15,047 patients with confirmed Sepsis disease from 2008 to 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) v1.0 database. The MIMIC-IV database is a comprehensive, de-identified clinical dataset originating from the Beth Israel Deaconess Medical Center in Boston, it includes extensive data on intensive care unit (ICU) patients, such as vital signs, lab results, and medication orders, spanning multiple years, accessible to researchers through an application process. AG can be obtained by direct extraction in the MIMIC-IV database (itemid = 50,868 from the laboratory events table of mimic_hosp), inclusion of AG values for the first test on first day of ICU admission. The patients were grouped into quartiles according to the AG interquartile range. The primary outcome was the 28-day mortality. Multiple logistic regression analysis was used to calculate the odds ratio (OR), while accounting for potential confounders, and the robustness of the results were evaluated in subgroup analyses. Among the 15,047 patients included in this study, the average age was 65.9 ±â€…16.0 years, 42.5% were female, 66.1% were Caucasian, and the 28-day mortality rate was 17.9% (2686/15,047). Multiple logistic regression analysis revealed the 28-day mortality in every increase of AG (per SD mEq/L), there is an associated 1.2 times (OR 1.2, 95% CI 1.12-1.29, P < .001) increase. Increased 28-day mortality (OR 1.53, 95% confidence interval 1.29-1.81, P < .001) in the group with the AG (15-18 mEq/L), and (OR 1.69, 95% confidence interval 1.4-2.04, P < .001) in the group with the highest AG (≥18 mEq/L), AG (<12 mEq/L) as a reference group, in the fully adjusted model. In adult patients with sepsis, the early AG at the time of ICU admission is an independent risk factor for prognosis.

The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms.

Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

The use of venous blood gas in assessing arterial acid-base and oxygenation status - an analysis of aggregated data from multiple studies evaluating the venous to arterial conversion (v-TAC) method.

BACKGROUND: Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria. RESEARCH DESIGN AND METHODS: We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits. RESULTS: 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (-0.029 to 0.031), PCO2 -0.08 (-0.65 to 0.49) kPa, and PO2 0.04 (-1.71 to 1.78) kPa, with similar values for all sub-group analyses. CONCLUSION: These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid-base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.

Diagnostic accuracy of the anion gap to identify toxic lithium concentrations: a single-center retrospective observational study.

INTRODUCTION: Lithium exhibits a narrow margin between therapeutic doses and toxic blood concentrations, which can pose a substantial risk of toxic effects. Reportedly, lithium toxicity may be associated with a reduced anion gap; however, the precise relationship remains unclear. This study examined several different anion gap calculation methods to detect toxic lithium concentrations without directly measuring blood lithium concentrations. METHODS: Our retrospective study analyzed blood samples collected for lithium concentration measurements. The anion gap was determined using three different methods, both with and without albumin and lactate concentration corrections. Samples were categorized into two groups based on lithium concentration (<1.5 or ≥1.5 mmol/L), and anion gap values were compared. Correlation and logistic regression analyses were used to assess the relationship between each anion gap indicator and lithium concentration. Receiver operating characteristic curves were used for diagnostic analysis. RESULTS: Overall, 24 measurements were collected, with 41.7% of samples falling within the toxic range. The high-lithium concentration group exhibited significantly smaller anion gaps. Correlation and logistic regression analyses revealed a significant association between anion gap values and lithium concentrations. Areas under the receiver operating characteristic curve were: conventional anion gap 0.77 (95% CI: 0.55-0.94); albumin-corrected anion gap 0.85 (95% CI: 0.66-1.00); and both albumin- and lactate-corrected anion gap 0.86 (95% CI: 0.66-1.00). DISCUSSION: The anion gap is calculated as the difference between measured cations and anions. Accumulation of lithium (a cation) may decrease measured cations and decrease the calculated anion gap. Abnormal albumin and lactate concentrations may also alter the anion gap and affect its usefulness as a diagnostic marker for elevated serum lithium concentrations. A negative likelihood ratio of 0.1 suggests that the anion gap might be valuable in excluding toxicity. CONCLUSIONS: The corrected anion gap, accounting for albumin and lactate concentrations, may be beneficial in suggesting the possibility of toxic lithium concentrations.

Independent variables of pH: Ten Knights of the Hydrogen Ion Kingdom-Part I. A prospective observational study.

CO2, HCO3, SID, and total weak acids have been defined as pH's independent variables. However, according to Gamble, HCO3 should be equal to the difference between the sum of cations and the sum of anions besides HCO3. Therefore, if this mathematical expression is substituted for HCO3 in the Henderson-Hasselbalch equation, all independent variables of pH can be demonstrated. Our aim is to test this theory in this study. This prospective observational study was conducted between 2019 and 2020. All admitted patients to the intensive care unit who were >18 years old were included. Demographic data, blood gas parameters, albumin, magnesium, and inorganic phosphorus levels, and outcomes were recorded twice (at admission and at the 24th hour). The multivariate linear regression model was used to determine pH's independent variables. In the multivariate linear regression model, pH was significantly increased by each unit increase in Na, K, Ca, and Mg (mmol L-1). In contrast, pH was significantly decreased by each unit increase in CO2, Cl, lactate, albumin (g dL-1), inorganic phosphorus (mg dL-1), and the strong ion gap. Ten independent variables can accurately predict the changes in pH. For this reason, all ten independent variables should be separately evaluated when interpreting the acid-base status. With this understanding, all algorithms regarding acid-base evaluation may become unnecessary.

Albumin corrected anion gap for predicting in-hospital death among patients with acute myocardial infarction: A retrospective cohort study.

OBJECTIVE: To explore the relationship between Anion Gap (AG), Albumin Corrected AG (ACAG), and in-hospital mortality of Acute Myocardial Infarction (AMI) patients and develop a prediction model for predicting the mortality in AMI patients. METHODS: This was a retrospective cohort study based on the Medical Information Mart for Intensive Care (MIMIC)-Ⅲ, MIMIC-IV, and eICU Collaborative Study Database (eICU). A total of 9767 AMI patients who were admitted to the intensive care unit were included. The authors employed univariate and multivariable cox proportional hazards analyses to investigate the association between AG, ACAG, and in-hospital mortality; p < 0.05 was considered statistically significant. A nomogram incorporating ACAG and clinical indicators was developed and validated for predicting mortality among AMI patients. RESULTS: Both ACAG and AG exhibited a significant association with an elevated risk of in-hospital mortality in AMI patients. The C-index of ACAG (C-index = 0.606) was significantly higher than AG (C-index = 0.589). A nomogram (ACAG combined model) was developed to predict the in-hospital mortality for AMI patients. The nomogram demonstrated a good predictive performance by Area Under the Curve (AUC) of 0.763 in the training set, 0.744 and 0.681 in the external validation cohort. The C-index of the nomogram was 0.759 in the training set, 0.756 and 0.762 in the validation cohorts. Additionally, the C-index of the nomogram was obviously higher than the ACAG and age shock index in three databases. CONCLUSION: ACAG was related to in-hospital mortality among AMI patients. The authors developed a nomogram incorporating ACAG and clinical indicators, demonstrating good performance for predicting in-hospital mortality of AMI patients.

Exploring the Influence of Acid-Base Status on Athletic Performance during Simulated Three-Day 400 m Race.

This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups-one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)-performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes' ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.

Hypocapnia in women with fibromyalgia.

OBJECTIVES: The purpose of this study was to investigate whether people with fibromyalgia (FM) have dysfunctional breathing by examining acid-base balance and comparing it with healthy controls. METHODS: Thirty-six women diagnosed with FM and 36 healthy controls matched for age and gender participated in this cross-sectional study. To evaluate acid-base balance, arterial blood was sampled from the radial artery. Carbon dioxide, oxygen, bicarbonate, base excess, pH and lactate were analysed for between-group differences. Blood gas analyses were performed stepwise on each individual to detect acid-base disturbance, which was categorized as primary respiratory and possible compensation indicating chronicity. A three-step approach was employed to evaluate pH, carbon dioxide and bicarbonate in this order. RESULTS: Women with FM had significantly lower carbon dioxide pressure (p = 0.013) and higher lactate (p = 0.038) compared to healthy controls at the group level. There were no significant differences in oxygen pressure, bicarbonate, pH and base excess. Employing a three-step acid-base analysis, 11 individuals in the FM group had a possible renally compensated mild chronic hyperventilation, compared to only 4 among the healthy controls (p = 0.042). CONCLUSIONS: In this study, we could identify a subgroup of individuals with FM who may be characterized as mild chronic hyperventilators. The results might point to a plausible dysfunctional breathing in some women with FM.

Changes in the hematobiochemical, acid-base and blood gas elements as well as biomarkers of inflammation and bone metabolism in donkeys (Equus asinus) with acute bleeding.

Background: Acute hemorrhage is fatal in equines with a complication of severe hypovolemic shock that causes a sudden death in such cases. Aim: This study was designed to report the influences of acute bleeding in conscious non-sedated donkeys (Equus asinus) on the hematobiochemical variables, acid-base, blood gas elements, and markers of inflammation and bone metabolism. Methods: Eight healthy donkeys were used where a total of 900 ml of whole blood was collected. Five blood samples were collected from each animal: just before collection of blood (T0); (2) 30 (T1), 60 (T2), 120 (T3), and 240 minutes (T4) later. The blood panels including total white blood cells, lymphocytes, neutrophils, red blood cell counts (RBCs), HCT, hemoglobin (Hg), and RBCs indices were measured. Biochemical parameters and electrolytes were evaluated. The activity of aspartate aminotransferase (AST), creatine kinase (CK), and γ-glutamyl transferase (GGT) were also determined. Complete acid-base and blood gas panels were assessed. Serum amyloid A (SAA), haptoglobin (Hp), osteocalcin (OC), bone alkaline phosphatase (b-ALP), and pyridinoline cross-links (PYD) were measured. Results: The RBCs, Hg, and HCT increased significantly at points T1, T2, and T3 compared to T0. The concentrations of total proteins and albumin decreased significantly at points T3 and T4. The blood urea nitrogen concentrations increased significantly at T4. Creatinine concentrations increased significantly at T2 and T3. The AST, GGT, and CK decreased significantly. On the other hand, glucose increased significantly at T3 and T4. The pH decreased significantly at points T1, T2, T3, and T4. The PCO2 increased significantly at T3 and T4. The BE, HCO3, and TCO2 values decreased significantly at T2, T3, and T4. Contrary, the AG increased significantly at points T3 and T4. The potassium increased significantly at T1-T4 and chloride decreased significantly at T3 and T4. Lactate showed significant increases at T1-T4. The SAA, Hp, OC, b-ALP, and PYD did not differ significantly at T1-T4. Conclusion: In conscious non-sedated donkeys, induced bleeding resulted in significant changes in the hematobiochemical elements, the acid-base status, and blood gas and electrolyte parameters. However, it did not change the markers of inflammation and bone metabolism.

[Comparison of different methods for monitoring of acid base status in dairy cow herds]. / Methodenvergleich zur Überwachung des Säuren-Basen-Status in Milchviehherden.

OBJECT AND PURPOSE: Acid-base disorders in dairy herds can be diagnosed by determining urinary net base excretion (NBE). Modifications of this method are the differential NBE (dNBE) with determination of the urinary concentration-independent base-acid ratio (BAR) and the simplified NBE test with reduced urine volume (sNBE). The aim of this study was to compare these methods among themselves and as a pooled test, in their assessment of cow group acid base status as well as to derive recommendations for practical use. ANIMALS, MATERIAL, AND METHODS: The concentrations of NBE, dNBE, and sNBE were measured in urine samples derived from 855 German-Holstein cows in 127 cow groups at different stages of lactation. BAR was then calculated. dNBE and BAR were determined both individually per cow and as a pool of a group. Mixed linear models were used to examine the relationship between the mean of the individual animal values and the pool sample result of a group for these two parameters. In addition, all groups were evaluated with respect to acidotic or alkalotic load based on their single animal results of the respective methods, the mean values formed from them, and the measured pool result. By using the single animal BAR as reference, the sensitivity and specificity of the different methods were calculated. RESULTS: The calculated mean values of the individual measurements of dNBE and BAR differed from the measured value in the pool sample, especially in low and high measurement ranges. In the group assessment, NBE showed the best combined sensitivity and specificity for the detection of acid base disorders. The dNBE pool assay showed satisfactory specificity with respect to acidosis and alkalosis, while the sNBE on an individual animal basis and the BAR determination in the pool showed satisfactory sensitivity with respect to acidosis. CONCLUSIONS AND CLINICAL RELEVANCE: It was shown that NBE determined in individual animal samples is well suited for the assessment of acid base status of cow groups and can therefore be recommended for practical use. The determination of dNBE as well as BAR as a pool test is not sufficient for the detection of alkalotic load in cow groups but may help to confirm an existing acidotic load.

Demystifying normal-anion-gap metabolic acidosis: pathophysiology, aetiology, evaluation and diagnosis.

Normal-anion-gap metabolic acidosis (NAGMA) is a common but often under-recognised and poorly understood condition, especially by less-experienced clinicians. In adults, NAGMA might be an initial clue to a more significant underlying pathology, such as autoimmune diseases, hypergammaglobulinemia or drug toxicities. However, identifying the aetiology can be challenging due to the diverse processes involved in the development of acidosis. A better understanding of the pathophysiology of NAGMA can help treating physicians suspect and evaluate the condition early and reach the correct diagnosis. This article provides an overview of renal acid-base regulation, discusses the pathophysiological processes involved in developing NAGMA and provides a framework for evaluation to reach an accurate diagnosis.

Decreases in Epoxide-Driven Secondary Organic Aerosol Production under Highly Acidic Conditions: The Importance of Acid-Base Equilibria.

Isoprene has the highest atmospheric emissions of any nonmethane hydrocarbon, and isoprene epoxydiols (IEPOX) are well-established oxidation products and the primary contributors forming isoprene-derived secondary organic aerosol (SOA). Highly acidic particles (pH 0-3) widespread across the lower troposphere enable acid-driven multiphase chemistry of IEPOX, such as epoxide ring-opening reactions forming methyltetrol sulfates through nucleophilic attack of sulfate (SO42-). Herein, we systematically demonstrate an unexpected decrease in SOA formation from IEPOX on highly acidic particles (pH < 1). While IEPOX-SOA formation is commonly assumed to increase at low pH when more [H+] is available to protonate epoxides, we observe maximum SOA formation at pH 1 and less SOA formation at pH 0.0 and 0.4. This is attributed to limited availability of SO42- at pH values below the acid dissociation constant (pKa) of SO42- and bisulfate (HSO4-). The nucleophilicity of HSO4- is 100× lower than SO42-, decreasing SOA formation and shifting particulate products from low-volatility organosulfates to higher-volatility polyols. Current model parameterizations predicting SOA yields for IEPOX-SOA do not properly account for the SO42-/HSO4- equilibrium, leading to overpredictions of SOA formation at low pH. Accounting for this underexplored acidity-dependent behavior is critical for accurately predicting SOA concentrations and resolving SOA impacts on air quality.

Responses of the blood acid-base balance and blood plasma metabolomics of broiler chickens after change to diets with high free amino acid levels.

Free amino acids (AA) are needed to fulfill the AA requirements of broiler chickens in diets low in CP. This study investigated whether the acid-base balance and the blood plasma metabolome are affected immediately after a change to diets with high free AA levels. Male broiler chickens received a starter diet with 164 g CP/kg and 80 g soy protein isolate/kg until d 7 post-hatch. From this day on, birds were offered a diet almost identical to the starter diet (0FAA) or 2 diets with 50% (50FAA) or 100% (100FAA) of the digestible AA from soy protein isolate substituted with free AA. Blood was sampled to determine the acid-base status and for untargeted metabolomics analysis on d 0, 1, 2, 4, 7, and 14 and d 1, 7, and 14 after diet change, respectively (n = 14 birds/treatment). Compared to 0FAA, blood pH was decreased on d 4 and 7 for 100FAA and on d 4 for 50FAA (P ≤ 0.019). On d 4, 7, and 14, bicarbonate, base excess, and total carbon dioxide were lower for 100FAA than for 0FAA (P ≤ 0.006). The partial pressure of carbon dioxide was higher for 50FAA than for 0FAA on d 4 (P = 0.047). Compared to 0FAA, chloride was higher for 100FAA on d 1, 2, 4, 7, and 14, and for 50FAA on d 1, 2, and 4 (P ≤ 0.030). In the metabolomics assay, 602, 463, and 302 metabolites were affected by treatment on d 1, 7, and 14, respectively (P < 0.050), but they did not indicate that metabolic pathways were affected. Flavonoids were the most consistently affected category of metabolites. The results indicated a metabolic acidosis for 100FAA from d 4 to 7 and a respiratory acidosis for 50FAA on d 4 after diet change. These types of acidosis were compensated later on in the experiment. The metabolomics analysis did not indicate that high free AA inclusion affected metabolic pathways.

Urine pH as predictor of blood acid-base status in dairy cattle fed acidogenic diets.

We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field conditions in cows fed acidogenic diets. Eighty-six cows were sampled for urine and blood. Urine pH was evaluated immediately after collection, and blood acid-base status was evaluated within 2 hours of collection using a portable blood analyzer. Twenty-five cows were classified as having severe metabolic acidosis (blood pH ≤ 7.4; bicarbonate < 24 mmol/L, base excess ≤ -0.5; PCO2 low to normal concentrations and urine pH between 4.88 and 5.71. There was a positive linear association between urine pH and blood pH (r = 0.46), and between urine pH and base excess (r = 0.74). The area under the ROC curve was 0.91 (CI 95 %= 0.84-0.96; good-excellent test). The optimal cut-off value for urine pH to categorize a cow with severe metabolic acidosis was 5.5 (94 % specificity and 72 % sensitivity). For each 0.1 unit of decrease in urine pH below 5.5, cows were 1.6 times (95 % CI= 1.3-2.1) more likely to exhibit a severe metabolic acidosis. We conclude that a urine pH of 5.5 or less is indicative of more life-threatening metabolic acidosis in dairy cows.

Acid accumulation is associated with metabolic alterations; higher energy, fat, and protein intake; and energy expenditure.

OBJECTIVE: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24-h energy expenditure (EE). METHODS: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Measurements included body composition by dual-energy x-ray absorptiometry scan, ad libitum energy intake by a vending machine paradigm over 3 days, and 24-h EE in a whole-room indirect calorimeter. RESULTS: Lower bicarbonate, higher AG, and higher CAG were correlated with higher waist and thigh circumferences, body fat (percentage), fat mass, triglycerides, and lower high-density lipoprotein cholesterol. Acid accumulation markers were correlated with higher total energy (CAG partial r = 0.17; p = 0.02), fat (CAG partial r = 0.17; p = 0.02), protein intake (CAG partial r = 0.20; p = 0.006), and 24-h EE (CAG partial r = 0.24; p = 0.0007). A mediation analysis of CAG and total energy intake found that 24-h EE was a partial mediator (40%), but the association remained significant (ß = 0.15; p < 0.0001). CONCLUSIONS: In healthy individuals, acid accumulation was associated with an unfavorable metabolic phenotype; higher 24-h EE; and increased total energy, fat, and protein intake. Acid accumulation markers, as putative markers of higher dietary acid load (e.g., from protein), may affect energy balance physiology promoting weight gain.

Base excess (BE): reloaded.

The base excess value (BE, mmol/L), not standard base excess (SBE), correctly calculated including pH, pCO2 (mmHg), sO2 (%) and cHb (g/dl) is a diagnostic tool for several in vivo events, e.g., mortality after multiple trauma or shock, acidosis, bleeding, clotting, artificial ventilation. In everyday clinical practice a few microlitres of blood (arterial, mixed venous or venous) are sufficient for optimal diagnostics of any metabolic acidosis or alkalosis.The same applies to a therapeutic tool-then referred to as potential base excess (BEpot)-for several in vitro assessments, e.g., solutions for infusion, sodium bicarbonate, blood products, packed red blood cells, plasma. Thus, BE or BEpot has been a parameter with exceptional clinical significance since 2007.

Mechanisms and physiological relevance of acid-base exchange in functional units of the kidney.

This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two primary organ systems correct deviations from the standard pH balance: the respiratory system via gas exchange and the kidneys via proton/bicarbonate secretion and reabsorption. Focusing on kidney functions, we describe the complexity of renal architecture and its challenges for experimental research. We address specific roles of different nephron segments (the proximal convoluted tubule, the loop of Henle and the distal convoluted tubule) in pH homeostasis, while explaining the physiological significance of ion exchange processes maintained by the kidneys, particularly the role of bicarbonate ions (HCO3-) as an essential buffer system of the body. The review will be of interest to researchers in the fields of physiology, biochemistry and molecular biology, which builds a strong foundation and critically evaluates existing studies. Our review helps identify the gaps of knowledge by thoroughly understanding the existing literature related to kidney acid-base homeostasis.